This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is designed to assess the prevalence of interval Vitamin D deficiency in patients not responding to therapy with bisphosphonates for the treatment of osteoporosis. Patients meeting pre-defined criteria of "non-response" will be screened for vitamin D deficiency, and in those cases where deficiency is found, will have vitamin D replaced in order to see if this restores response to bisphosphonates. [unreadable]Bisphosphonates[unreadable] are a class of medications used to treat weak bones or [unreadable]osteoporosis[unreadable]. A special type of x-ray known as a [unreadable]DEXA Scan[unreadable] is usually done annually to see whether patients are responding to these medicines. Normally, there is an increase in the density of the bones (BMD) while on these medicines. A decline in bone density while on bisphosphonate treatment suggests a separate so-called [unreadable]secondary[unreadable] cause of osteoporosis may have developed. One such secondary cause is the development of vitamin D insufficiency. The purpose of this study is to answer the following two questions: 1. What is the frequency of vitamin D deficiency in patients who have had a decline in BMD? 2. In patients with vitamin D deficiency and a decline in BMD, does replacement of vitamin D cause a rebound increase in BMD ? It is expected that the study will determine the prevalence of vitamin D insufficiency in a group of patients whose bone health is dependent on the administration of bisphosphonates. It is also anticipated that in those patients who have low vitamin D, replacing it will improve their BMD. We believe that the proposed research questions can be answered in the setting of standard patient care. That is to say, this research will not require any interventions or procedures beyond what is normally required in a bone clinic. In addition to its role in bone health, vitamin D plays a key role in our immune system, helping fight infection. Accordingly, as a separate study, we wish to study the white blood cells of stored samples of blood to analyze gene changes before and after treatment with vitamin D. We can do this with samples of blood collected for clinical reasons.